Modulatory effects of levodopa on cognitive control in young but not in older subjects: a pharmacological fMRI study.

Older individuals show decline of prefrontal cortex (PFC) functions which may be related to altered dopaminergic neurotransmission. We investigated the effects of aging and dopaminergic stimulation in 15 young and 13 older healthy subjects on the neural correlates of interference control using fMRI. In a double-blind, placebo-controlled within-subject design, subjects were measured after levodopa (100 mg) or placebo administration. In each session, subjects performed a visual-spatial interference task based on a Stroop/Simon-like paradigm. Across age groups, interference (incongruent relative to congruent trials) was associated with activations in the presupplementary motor area, ACC, and intraparietal cortex. Increased interference was found behaviorally in older volunteers. Differential activation in left dorsolateral PFC in young subjects and bilateral PFC activity in older subjects was observed to be associated with interference control. Performance deteriorated under levodopa only in young subjects. This was accompanied by an increase of neural activity in ACC (p < .05; small-volume correction for multiple comparisons). Worsening of performance under levodopa in young subjects and the associated effect on ACC may indicate that overstimulation of the dopaminergic system compromises interference control. This supports the inverted-U-shaped model of neurotransmitter action.

Disentangling the prefrontal network for rule selection by means of a non-verbal variant of the Wisconsin Card Sorting Test.

This study disentangles the prefrontal network underlying executive functions involved in the Wisconsin Card Sorting Test (WCST). During the WCST, subjects have to perform two key processes: first, they have to derive the correct sorting rule for each trial by trial-and-error, and, second, they have to detect when this sorting rule is changed by the investigator. Both cognitive processes constitute key components of the executive system, which is subserved by the prefrontal cortex. For the current fMRI experiment, we developed a non-verbal variant of the WCST. Subjects were instructed either to respond according to a given sorting rule or to detect the correct sorting rule, like in the original version of the WCST. Data were obtained from 14 healthy male volunteers and analysed using SPM and a random effects model. All conditions activated a fronto-parietal network, which was generally more active when subjects had to search for the correct sorting rule than when the rule was announced beforehand. Significant differences between these two conditions were seen in the dorsolateral prefrontal cortex (PFC) and the parietal lobe. In addition, the data provided new evidence for the assumption of differentiated roles of the left and right prefrontal cortex. Although the right PFC showed a general involvement in response selection and the execution of goal directed responses, based on given rules, the left PFC was only activated when inductive reasoning and feedback integration was required.

Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test.

The specific role of particular cerebral regions with regard to executive functions remains elusive. We conducted a functional magnetic resonance imaging (fMRI) study to segregate different network components underlying the Wisconsin Card Sorting Test (WCST), a test widely applied clinically to assess executive abilities. Three different test variants of the WCST, differing in task complexity (A > B > C), were contrasted with a high-level baseline condition (HLB). Cognitive subcomponents were extracted in a serial subtraction approach (A-C, A-B, B-C). Imaging data were further subjected to a correlational analysis with individual behavioral parameters. Contrasting A with the HLB revealed the entire neural network underlying WCST performance, including frontoparietal regions and the striatum. Further analysis showed that, within this network, right ventrolateral prefrontal cortex related to simple working memory operations, while right dorsolateral prefrontal cortex related to more complex/manipulative working memory operations. The rostral anterior cingulate cortex (ACC) and the temporoparietal junction bilaterally represented an attentional network for error detection. In contrast, activation of the caudal ACC and the right dorsolateral prefrontal cortex was associated with increased attentional control in the context of increasing demands of working memory and cognitive control. Non-frontal activations were found to be related to (uninstructed relative to instructed) set-shifting (cerebellum) and working memory representations (superior parietal cortex, retrosplenium). The data provide neural correlates for the different cognitive components involved in the WCST. They support a central role of the right dorsolateral prefrontal cortex in executive working memory operations and cognitive control functions but also suggest a functional dissociation of the rostral and caudal ACC in the implementation of attentional control.